Esmolol hydrochloride (methyl-3-[4-(2-hydroxy-3-isopropylamino)propoxy]phenylpropionate hydrochloride) is a 50:50 racemic mixture of S- and R-isomers. Esmolol hydrochloride is a fast-onset beta-blocker used for treatment of cardiac disorders, such as tachycardia and hypertension. Most currently available beta-blockers have relatively long onset times. However, it is often desirable in the critical care setting to quickly reduce heart rate and/or improve rhythmicity during a cardiac crisis, e.g., during or shortly after a myocardial infarction. Conventional beta-blocking agents can be employed for such treatment, but their relatively long onset times can prevent a clinician from effectively titrating the dose quickly, e.g., when a patient is in crisis. Esmolol hydrochloride is particularly useful when treating a patient experiencing a cardiac crisis. Because of its relatively fast onset time, feedback is immediate and thus dosing can be adjusted quickly according to the patient's response.
Esmolol hydrochloride differs from conventional beta-blocking compounds in that it contains an ester functional group which can be rapidly hydrolyzed. Esmolol hydrochloride has a short duration in vivo due to the presence of the ester group and is indicated for the rapid control of ventricular rate in patients with supraventricular tachycardia (i.e., atrial fibrillation or atrial flutter) in perioperative, postoperative, or other emergent circumstances where short term control of ventricular rate with a short-acting agent is desirable. Esmolol hydrochloride is also indicated for intraoperative and postoperative tachycardia and/or hypertension. Esmolol hydrochloride is typically administered by infusion. A significant number of patients experience venous irritation at the infusion site. See Esmolol Hydrochloride Injection Ready-to-use 10 mL Vials, packaging insert (Baxter Healthcare Corporation). The incidence and amount of venous irritation observed in patients increases along with the concentration of the dose of esmolol hydrochloride administered. Id. Therefore, a desired higher infusion concentration often cannot be used to lower the heart rate of a patient in stress because of concern that significant venous irritation may develop. As a result, effective esmolol hydrochloride administration often takes longer than it otherwise would if higher infusion concentrations were administered.
In view of the foregoing, it would be advantageous to retain the efficacious beta-blockade effects of esmolol hydrochloride while minimizing the bothersome venous irritation that occurs with significant frequency in esmolol hydrochloride administration.